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Cajals Principles
(5)
- 1. The neuron is the elementary signaling unit
- 2. Neuron has dynamic polarization ->allows circutry flow
- 3. Defined the synapse (area of connection)
- 4. Connection specificity (only connect to one part)
- 5. Synaptic Plasticity - the connections in the brain can be modified by experience
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Main signal recording
- Recorded by cathode ray oscilloscope
- microelectrodes and macroelect.
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EEG
- 1st recorded with macroelectrodes (brain mapping) = receptotopic mapping
- - shows abnormalities but cant tell what is wrong
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Peripheral Nerve Recordings
alpha, beta, gama = mylenated (faster and thicker)
c = unmylenated = slower/thinner
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Nerve recruitment
Large(fast) to small (slower)
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Electrical recordings
- Excellent with time
- bad with location
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Type and tissue: EEG
Cortex
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Type and tissue: ERP/SEP
Sensory Motor Pathway
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Type and tissue: Whole nerve potential
peripheral Nerve
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Type and tissue: EMG
Skeletal Muscle
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Fast electrical membrane communication
- only plasma membrane involved
- - direct and indirect STP's
- -STP's are ATP dependent
- -Nerve voltages are either Graded or all or none
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Graded Potentials
- Passive - Ligand gated
- - occur in dendrite and soma
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All or None
- Active regenerative propogation - voltage gated
- - occur at AH-IS, axon, axon terminal
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Neuron electrophysiological techn.
(where to put the clamps)
- 1. extracellular
- 2. intracellular
- 3. Patch clamp recordings
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Patch Clamp recording
- -Recording ion channels
- -post synaptic membrane
- -in vitro
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Sherrington Discovered
- - synaptic delay
- - spinal reflexes
- - excitatory/inhibitory responses
soup/chemical vs sparks/electrical debate
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Membrane electrophysiology
membrane is permeable to lipids but not to cation/anions
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cations and anions can cross membrane by:
- 1. slow - transport membrane protiens
- 2. rapid - ion channels*
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Ion channels
- Passive - leakage
- Active - graded, all or none, neurosecretion
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passive ion channels
- Leakage
- - always open
- - responsible for RMP
- - single ion selective *
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Active ion channels
- Graded/ all or none/ neurosecretion
- - opened or closed (by voltage.ligands, sensory stimuli
- - have both single and multiple ion selectivities
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Ion distribution
Na, Cl,Ca - more outside
k - more inside
Actively distributed
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actively distributed Na K pump
- ATP needed
- - 3 Na out
- -2 K in
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Diffusional force
concentration across a barrier
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Electrochemical force
like ionic charges repel, unlike attract
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Intracellular membrane voltage
- set closest to the E ion of the most permeable ion
- RMP is -70 due to K
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RMP #'s
- same for one cell but varies from cell to cell
- small neurons = -55
- muscle =-80
- glial = -90
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Glial cells RMP
purels based on K+ diffusion, doesnt generate electrical signals
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RMP in neurons and Muscle cells
- Predominantely K+ leaking out
- some Na+ leakage in
Ca and Cl dont contribute to RMP
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Leak ion channels
- -Always open
- -single ion specific
- -placed all throughout the entire cell/neuron
- - more channels for K>Cl>Na
- - produce the "bacground" against all other electrical signals
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Ligand-gated Channels
:STP's
- Graded Synaptic potentials - EPSP / IPSP
- Ionotropic (direct /fast)
- metabotrophic (indirect/ slow)
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Location and Event: Dendrites and Body/soma
graded synaptic events
TRANSDUCTION
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Location and Event: A.H. and TZ
AP generation
TRANSFORMATION
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Location and Event: Axon
Impulse conduction
PROPAGATION
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Location and Event: Axon terminal
neurosecretion
TRANSLATION
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Temporal summation
same cell fires 2x in a row
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Spatial summation
2 cells fire at the same time
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Sutherland discovered
ionotrophic and metabotrophic STPs
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Ionotrophic STP
- direct/ fast
- - rapid/reversible
- - newer
- - due to direct selective ligand binding
- - can open/close ion channels
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Metabotrophic STP
- slow, gated ion channels
- - cascade needs to occur
- - many target substrates
- - old
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conductance
- increased G = gate opening
- decreaded G = gate closing
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Post synaptic membrane EPSP
- CAMs - neurexins and neurligands **
- ionotrophic STP - middle of the synapse
- metabotrophic stp - outside, surround iono
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passive electronic decay
as the epsp/ipsp travels through the cell body to AH it will degrade, if it doesnt reach threshold by AH then no AP
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IPSP
- hyperpolarization = increase negativity
- graded- temporal vs spatial summation
- both ionotrophic and metabotrophic
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Post synaptic membrane - IPSP
- CAMs - neurexins and neurligands
- ionotrophic STP -> gaba A*
- metabotrophic STP -> gaba b*
- also have passive decay
ionotrophic receptors are still in the middle of metabotrophic, but there are two rings of receptors
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TRIGGER ZONE
aka Axon hillock
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Eccles Discovered
the winner takes all idea, integration of epsp and ipsp
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Excitatory AA
- 75% glutamate
- 25% other NT (ACH, NA,serotonin)
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Hodgkin - Huxely model
sodium potasium duct* - timed sequence of 2 different ion selective channels
- 1. Na triggers depolarizating phase- into cell
- 2. K repolarize membrane back to RMP - moving out of cell
these are measured by patch clamp
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NA/K channels
- have:
- - ion selectivity
- - voltage sensitive/ regenerative/ able to propogate
- - have a refractory/inactive period, cant summate spikes
- - can be blocked by toxins
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Absolute refactiveness
- inactivation of voltage gated channels
- - after S1, s2 fails to form an A.P.
- - all Na and K channels are closed
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Relative refractiveness
- -When s2 fails to elicit a normal sized impulse
- - some channels opened, but not all
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Sodium and Potassium voltage channels (NaV) (Kv)
- specifically located-
- -at AH
- -entire length of unmylenated axon
- - nodes of ranvier
- -pre synaptic terminal membrane of myelinated
- -sarcolemma
- -t-tubule
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LCC
Local cation current - caused by Na influx, depolarizes
- - speed of propogation depends on fiber type
- increase axon size = decre resistance = faster
- small =unmylenated
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Large Myelinated Axons
- use Saltatory conduction
- impulses are regenerated at nodes of ranvier
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Neuron
- fastest 0.5 ms
- na in k out
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skeletal muscle
- 4 ms, slowest
- na in k out
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cardiac muscle
- 4 ms, slowest
- na and ca in, k out *
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visceral smooth muscle
- 1 ms, 2nd fastest
- ca in k out *
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Neurosecretion
- single impulse causes release of small neurotransmitters
- -glu, gaba, ach
LCC travels to azon terminal, opens Ca voltage gated channel, the ca triggers STP to release NT's
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quantal hypothesis
single impulses force small vesicles to release contents into synaptic cleft -> bind with ligand gated ion channels
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Repolarizing and reuptake
stop the release of ca and stop the release of NT
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3 types of voltage gated channels
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1 quanta
1 batch of NT raise by 1 mv
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quanta release dependent on:
ca concentration, more = more release
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Dale's rule
a single neuron releases same chemical signals at all of its synaptic terminals
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Presynaptic inhibiton and facilitation
- aka neuromodulation
- - inhibit = decrease NT release
- - facilitation = increase release
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Excitatory Synapses
- Grey type 1
- EAA = glu
- wide synaptic cleft
- fast or slow
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Inhibitory synapses
- Grey type 2
- IAA - gaba
- narrow synaptic cleft
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Ionotrophic EPSP
- Ampa R
- increase G
- NA flows in
- depolarization
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Metabotrophic EPSP
- mGlu-R
- neuropeptide transmitter
- decrease G
- k stays in
- depolarization
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Ionotrophic IPSP
- Gaba -a
- increase G
- increase Cl in
- hyperpolarization
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Metabotrophic IPSP
- gaba - b
- increase G
- increase K out
- hyperpolarization
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All or none LAW
- - triggered at a standard threshold voltage
- - have a standard magnitude
- - standard duration
- -standard voltage waveform
- -conduct or propagate at a constant speed
- -electrogenic- ability to self regenerate
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